Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV002510709 | SCV002820240 | uncertain significance | Spastic paraplegia-severe developmental delay-epilepsy syndrome | criteria provided, single submitter | clinical testing | The missense variant p.L117S in HACE1 (NM_020771.3) has not been reported previously as a pathogenic variant nor asa benign variant, to our knowledge.The p.L117S variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000Genomes.There is a large physicochemical difference between leucine and serine, which is likely to impact secondary proteinstructure as these residues differ in polarity, charge, size and/or other properties.The p.L117S missense variant is predicted to be damaging by both SIFT and PolyPhen2.The leucine residue at codon 117 of HACE1 is conserved in all mammalian species.The nucleotide c.350 in HACE1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates.For these reasons, this variant has been classified as Uncertain Significance. |